Pyrroline-5-carboxylate reductase 3 (PYCRL)

The protein contains 274 amino acids for an estimated molecular weight of 28663 Da.

 

Enzyme that catalyzes the last step in proline biosynthesis. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). PYCRL is exclusively linked to the conversion of ornithine to proline. (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 30

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VariantDescription
dbSNP:rs11549789
dbSNP:rs2242089
dbSNP:rs2242090

No binding partner found

The reference OMIM entry for this protein is 616408

Pyrroline-5-carboxylate reductase-like; pycrl
Pyrroline-5-carboxylate reductase 3; pycr3

DESCRIPTION

PYCRL (EC 1.5.1.2) is a cytosolic enzyme that catalyzes the final step of proline biosynthesis and reduces pyrroline-5-carboxylate (P5C) to L-proline using NADH as cofactor (De Ingeniis et al., 2012).

CLONING

De Ingeniis et al. (2012) reported that PYCRL is about 40 amino acids shorter at the C terminus compared with PYCR1 (179035) and PYCR2 (616406). It shares about 45% similarity with PYCR1 and PYCR2. Western blot analysis of fractionated Lu1205 human melanoma cells revealed that PYCRL is a cytosolic protein, whereas PYCR1 and PYCR2 are mitochondrial.

GENE FUNCTION

Proline can be synthesized beginning with glutamate or ornithine, and both pathways converge with the synthesis of the PYCR substrate P5C. Using Western blot analysis, De Ingeniis et al. (2012) found that Lu1205 cells had relatively high expression of PYCR1, PYCR2, and PYCRL. Knockdown of PYCR1 and PYCR2 in Lu1205 cells via small interfering RNA reduced the ratio of proline to glutamate, indicating that PYCR1 and PYCR2 both contribute to biosynthesis of proline from glutamate. In contrast, knockdown of PYCRL decreased the ratio of proline to ornithine, indicating that PYCRL is involved in the ornithine route of proline synthesis. PYCR1 showed a small contribution to proline synthesis via the ornithine route. De Ingeniis et al. (2012) concluded that PYCRL is used exclusively for biosynthesis of proline from ornithine.

MAPPING

De Ingeniis et al. (2012) reported that the PYCRL gene maps to chromosome 8q24.3. ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616408 was added.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.